Neisseria meningitidis is a Gram-negative human pathogen [1] which causes bacterial meningitis. It is closely related to N. gonorrhoeae, although one feature that clearly differentiates meningococcus is the presence of a polysaccharide capsule that is present in all pathogenic meningococci.
Based on the organism's capsular polysaccharide, twelve serogroups of N. meningitidis have been identified (A, B, C, H, I, K, L, 29E, W135, X, Y & Z). Serogroup A (‘MenA’) is most common cause of epidemic disease in sub-Saharan Africa. Serogroups B & C are responsible for the majority of cases in developed countries, with the remaining cases being caused by serogroups W135 & Y.
As well as being used for classification, the capsular polysaccharide has been used for vaccination. An injectable tetravalent vaccine of capsular polysaccharides from serogroups A, C, Y & W135 has been known for many years [2,3] and is licensed for human use. Although effective in adolescents and adults, it induces a poor immune response and short duration of protection and cannot be used in infants [e.g. 4]. The polysaccharides in this vaccine are unconjugated and are present at a 1:1:1:1 weight ratio [5]. MENCEVAX ACWY™ and MENOMUNE™ both contain 50 μg of each purified polysaccharide once reconstituted from their lyophilized forms. The capsular saccharides of serogroups A, C, W135 & Y have also been combined in the form of conjugates [6-9] to give tetravalent vaccines e.g. the unadjuvanted MENACTRA™ product.
Conjugated serogroup C oligosaccharides have been approved for human use, including MENJUGATE™ [10,11], MENINGITEC™ and NEISVAC-C™. The MENJUGATE™ and MENINGITEC™ products have oligosaccharide antigens conjugated to a CRM197 carrier, whereas NEISEVAC-C™ uses the complete polysaccharide (de-O-acetylated) conjugated to a tetanus toxoid carrier.
There remains, however, a need for improvements in conjugate vaccines against serogroups A, W135 and Y, and in their manufacture. That need is addressed by the products, processes and uses disclosed in reference 7, but there remains scope for further modifications and improvements.